tbuckley/cabot-search huggingface dataset:
Characterization of immune exhaustion and suppression in the tumor microenvironment of splenic marginal zone lymphoma
Authors: Theodora Anagnostou, Zhi-Zhang Yang, Shahrzad Jalali, Hyo Jin Kim, Daniel P. Larson, Xinyi Tang, Yue Yu, Joshua C. Pritchett, Jose Villasboas Bisneto, Tammy L. Price-Troska, Patrizia Mondello, Anne J. Novak, Stephen M. Ansell
Journal: Leukemia (2023)
Racial and Ethnic Disparities in Outcomes Among Newborns with Congenital Diaphragmatic Hernia
Authors: Shelby R. Sferra, Pooja S. Salvi, Annalise B. Penikis, Jennine H. Weller, Joseph K. Canner, Matthew Guo, Abigail J. Engwall-Gill, Daniel S. Rhee, Joseph M. Collaco, Amaris M. Keiser, Daniel G. Solomon, Shaun M. Kunisaki
Journal: JAMA Network Open (2023)

Importance There is some data to suggest that racial and ethnic minority infants with congenital diaphragmatic hernia (CDH) have poorer clinical outcomes. Objective To determine what patient- and institutional-level factors are associated with racial and ethnic differences in CDH mortality. Design, Setting, and Participants Multicenter cohort study of 49 US children’s hospitals using the Pediatric Health Information System database from January 1, 2015, to December 31, 2020. Participants were patients with CDH admitted on day of life 0 who underwent surgical repair. Patient race and ethnicity were guardian-reported vs hospital assigned as Black, Hispanic (White or Black), or White. Data were analyzed from August 2021 to March 2022. Exposures Patient race and ethnicity: (1) White vs Black and (2) White vs Hispanic; and institutional-level diversity (as defined by the percentage of Black and Hispanic patients with CDH at each hospital): (1) 30% or less, (2) 31% to 40%, and (3) more than 40%. Main Outcomes and Measures The primary outcomes were in-hospital and 60-day mortality. The study hypothesized that hospitals managing a more racially and ethnically diverse population of patients with CDH would be associated with lower mortality among Black and Hispanic infants. Results Among 1565 infants, 188 (12%), 306 (20%), and 1071 (68%) were Black, Hispanic, and White, respectively. Compared with White infants, Black infants had significantly lower gestational ages (mean [SD], White: 37.6 [2] weeks vs Black: 36.6 [3] weeks; difference, 1 week; 95% CI for difference, 0.6-1.4; P &amp;amp;lt; .001), lower birthweights (White: 3.0 [1.0] kg vs Black: 2.7 [1.0] kg; difference, 0.3 kg; 95% CI for difference, 0.2-0.4; P &amp;amp;lt; .001), and higher extracorporeal life support use (White: 316 patients [30%] vs Black: 69 patients [37%]; χ 2 1 = 3.9; P = .05). Black infants had higher 60-day (White: 99 patients [9%] vs Black: 29 patients [15%]; χ 2 1 = 6.7; P = .01) and in-hospital (White: 133 patients [12%] vs Black: 40 patients [21%]; χ 2 1 = 10.6; P = .001) mortality . There were no mortality differences in Hispanic patients compared with White patients. On regression analyses, institutional diversity of 31% to 40% in Black patients (hazard ratio [HR], 0.17; 95% CI, 0.04-0.78; P = .02) and diversity greater than 40% in Hispanic patients (HR, 0.37; 95% CI, 0.15-0.89; P = .03) were associated with lower mortality without altering outcomes in White patients. Conclusions and Relevance In this cohort study of 1565 who underwent surgical repair patients with CDH, Black infants had higher 60-day and in-hospital mortality after adjusting for disease severity. Hospitals treating a more racially and ethnically diverse patient population were associated with lower mortality in Black and Hispanic patients.
Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromas
Authors: Andrea M Gross, Eva Dombi, Pamela L Wolters, Andrea Baldwin, Anne Dufek, Kailey Herrera, Staci Martin, Joanne Derdak, Kara S Heisey, Patricia M Whitcomb, Seth M Steinberg, David J Venzon, Michael J Fisher, AeRang Kim, Miriam Bornhorst, Brian D Weiss, Jaishri O Blakeley, Malcolm A Smith, Brigitte C Widemann
Journal: Neuro-Oncology (2023)

Abstract Background Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies. Methods This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index). Results For the 74 children (median age 10.3 years; range 3–18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1–100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment. Conclusions With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues.
Multifunctional Double‐Layer and Dual Drug‐Loaded Microneedle Patch Promotes Diabetic Wound Healing
Authors: Wei Liu, Xingxing Zhai, Xue Zhao, Yongjie Cai, Xinmei Zhang, Kai Xu, Jie Weng, Jianshu Li, Xingyu Chen
Journal: Advanced Healthcare Materials (2023)

Chronic nonhealing diabetic wounds are a serious complication of diabetes, with a high morbidity rate that can cause disability or death. The long period of inflammation and dysfunctional angiogenesis are the main reasons for wound-healing difficulty in diabetes. In this study, a multifunctional double-layer microneedle (DMN) is constructed to control infection and promote angiogenesis, meeting the multiple demands of the healing process of a diabetic wound. The double-layer microneedle is consisted in a hyaluronic acid substrate and a mixture of carboxymethyl chitosan and gelatin as the tip. The antibacterial drug tetracycline hydrochloride (TH) is loaded into the substrate of the microneedle to achieve rapid sterilization and promote resistance to external bacterial infections. The microneedle tip loaded with recombinant human epidermal growth factor (rh-EGF) is inserted into the skin, in response to gelatinase produced by resident microbe and disassociate to achieve the enzymatic response release. The double-layer drug-loaded microneedles (DMN@TH/rh-EGF) have antibacterial and antioxidant effects, and promote cell migration and angiogenesis in vitro. In an in vivo diabetic wound model, using rats, the DMN@TH/rh-EGF patch is able to inhibit inflammation, promote angiogenesis, collagen deposition, and tissue regeneration during the wound healing process, promoting its healing.
Sex Differences in Cardiac Troponin Trajectories Over the Life Course
Authors: Marie de Bakker, Atul Anand, Martin Shipley, Takeshi Fujisawa, Anoop S.V. Shah, Isabella Kardys, Eric Boersma, Eric J. Brunner, Nicholas L. Mills, Dorien M. Kimenai
Journal: Circulation (2023)

Cardiac troponin concentrations are lower in women than men. We examined whether age- and risk factor-related changes in cardiac troponin over the life course differ by sex and if the trajectory of cardiac troponin was informative in respect of cardiovascular outcomes in women and men in the general population.
Online support improved eczema symptoms in children and young people
Authors: Helen Saul, Samantha Cassidy, Candace Imison, Miriam Santer
Journal: BMJ (2023)

The study Santer M, Muller I, Becque T. Eczema Care Online behavioural interventions to support self-care for children and young people: two independent, pragmatic, randomised controlled trials. BMJ 2022;379:e072007. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/online-support-improved-eczema-symptoms-in-children-and-young-people/
Effects of newer kidney protective agents on kidney endpoints provide implications for future clinical trials
Authors: Hiddo J.L. Heerspink, Niels Jongs, Brendon L. Neuen, Patrick Schloemer, Muthiah Vaduganathan, Lesley A. Inker, Robert A. Fletcher, David C. Wheeler, George Bakris, Tom Greene, Glenn M. Chertow, Vlado Perkovic
Journal: Kidney International (2023)

Doubling of serum creatinine (equivalent to a 57% decline in the estimated glomerular filtration rate (eGFR)) is an accepted component of a composite kidney endpoint in clinical trials. Smaller declines in eGFR (40%, 50%) have been applied in several recently conducted clinical trials. Here, we assessed the effects of newer kidney protective agents on endpoints including smaller proportional declines in eGFR to compare relative event rates and the magnitude of observed treatment effects. We performed a post hoc analysis of 4401 patients in the CREDENCE, 4304 in the DAPA-CKD, 5734 in the FIDELIO-DKD, and 3668 in the SONAR trials, which assessed the effects of canagliflozin, dapagliflozin, finerenone and atrasentan in patients with chronic kidney disease. Effects of active therapies versus placebo on alternative composite kidney endpoints incorporating different eGFR decline thresholds (40%, 50%, or 57% eGFR reductions from baseline) with kidney failure or death due to kidney failure were compared. Cox-proportional hazards regression models were used to assess and compare treatment effects. During follow-up, event rates were higher for endpoints incorporating smaller versus larger eGFR decline thresholds. Compared to the treatment effects on kidney failure or death due to kidney failure, the magnitude of relative treatment effects was generally similar when considering composite endpoints incorporating smaller declines in eGFR. Hazard ratios for the four interventions ranged from 0.63 to 0.82 for the endpoint incorporating 40% eGFR decline and 0.59 to 0.76 for the endpoint incorporating 57% eGFR decline. Clinical trials incorporating a 40% eGFR decline in a composite endpoint would require approximately half the number of participants compared to a 57% eGFR decline with equivalent statistical power. Thus, in populations at high risk of CKD progression, the relative effects of newer kidney protective therapies appear generally similar across endpoints based on varying eGFR decline thresholds.
Kratom-induced acute liver injury: A case study and the importance of herbal supplement regulation
Authors: Katerina Roma, Salman Mohammed, Blake Sieck, Katrina Naik, Shahid Wahid
Journal: Journal of Hepatology (2023)

Alternative medicine supplements have become the second most common cause of drug-induced liver injury (DILI) in the US. Kratom is a herbal supplement that is popular for its psychotropic and opioid-like activity. It has become increasingly available in western countries, which often have no specific regulations on its use. However, reports of adverse events linked to kratom use have been increasing; it has been implicated in acute liver injury (mostly cholestatic), acute liver failure, organ dysfunction, toxicity, coma, seizures, and death. Herein, we aim to increase healthcare provider and public awareness of the risks posed by kratom and ultimately support increased regulation of its use.
Ruth Scherz-Shouval: Together we can ask big questions
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2023)

Ruth Scherz-Shouval is an Assistant Professor in the Department of Biomolecular Sciences at the Weizmann Institute of Science, Israel. Her lab is interested in the tumor microenvironment, how stress responses can shape the tumor microenvironment, and also how different cells within the tumor microenvironment interact. We talked about how her interest in science began at an early age, the impact of having strong female role models, and ways to encourage collaboration and create an engaging and welcoming lab environment.
Nanoparticle-based immunotherapeutics: From the properties of nanocores to the differential effects of administration routes
Authors: André Perez-Potti, Manuel Rodríguez-Pérez, Ester Polo, Beatriz Pelaz, Pablo del Pino
Journal: Advanced Drug Delivery Reviews (2023)

The engagement with the immune system is one of the main cornerstones in the development of nanotechnologies for therapy and diagnostics. Recent advances have made possible the tuning of features like size, shape and biomolecular modifications that influence such interactions, however, the capabilities for immune modulation of nanoparticles are still not well defined and exploited. This review focuses on recent advances made in preclinical research for the application of nanoparticles to modulate immune responses, and the main features making them relevant for such applications. We review and discuss newest evidence in the field, which include in vivo experiments with an extensive physicochemical characterization as well as detailed study of the induced immune response. We emphasize the need of incorporating knowledge about immune response development and regulation in the design and application of nanoparticles, including the effect by parameters such as the administration route and the differential interactions with immune subsets.
An atlas of the bone marrow bone proteome in patients with dysproteinemias
Authors: Matthew Ho, Surendra Dasari, Alissa Visram, Matthew T. Drake, M. Cristine Charlesworth, Kenneth L. Johnson, Ganesh P. Pujari, Dragan Jevremovic, Taxiarchis Kourelis
Journal: Blood Cancer Journal (2023)

Abstract Multiple myeloma (MM) bone disease is a significant cause of morbidity but there is a paucity of data on the impact of malignant plasma cells on adjacent trabecular bone within the BM. Here, we characterize the proteome of trabecular bone tissue from BM biopsies of 56 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM), newly diagnosed (NDMM), relapsed MM (RMM), and normal controls. Proteins involved in extracellular matrix (ECM) formation and immunity pathways were decreased in SMM and active MM. Among the proteins most decreased were immunoglobulins, type IV collagen, and TIMP3, suggesting increased immunoparesis and decreased ECM remodelling within trabecular bone. Proteins most increased in SMM/MM were APP (enhances osteoclast activity), ENPP1 (enhances bone mineralization), and MZB1 (required for normal plasmablast differentiation). Pathway analyses showed that proteins involved in gamma -carboxylation, a pathway implicated in osteocalcin function, osteoblast differentiation, and normal hematopoiesis, were also overexpressed in SMM/MM. This study is the first comprehensive proteomic atlas of the BM bone proteome in dysproteinemias. We identify new key proteins and pathways for MM bone disease and potentially impaired hematopoiesis, and show for the first time that gamma -carboxylation pathways are increased in the bone tissue of SMM/MM.
Comparative efficacy of biologics and oral agents in palmoplantar psoriasis and palmoplantar pustulosis: A systematic review and network meta-analysis of randomized clinical trials
Authors: Riley K. Spencer, Joy Q. Jin, Kareem G. Elhage, Mitchell S. Davis, Marwa Hakimi, Tina Bhutani, Wilson Liao
Journal: Journal of the American Academy of Dermatology (2023)
Molecular markers of metastatic disease in KRAS-mutant lung adenocarcinoma
Authors: D. Boiarsky, C.A. Lydon, E.S. Chambers, L.M. Sholl, M. Nishino, F. Skoulidis, J.V. Heymach, J. Luo, M.M. Awad, P.A. Janne, E.M. Van Allen, D.A. Barbie, N.I. Vokes
Journal: Annals of Oncology (2023)

Prior studies characterized the association of molecular alterations with treatment-specific outcomes in KRAS-mutant (KRAS
Comparison of HAV and HCV infections in vivo and in vitro reveals distinct patterns of innate immune evasion and activation
Authors: Ombretta Colasanti, Rani Burm, Hao-En Huang, Tobias Riedl, Jannik Traut, Nadine Gillich, Teng-Feng Li, Laura Corneillie, Suzanne Faure-Dupuy, Oliver Grünvogel, Danijela Heide, Ji-Young Lee, Cong Si Tran, Uta Merle, Maria Chironna, Florian F.W. Vondran, Katharina Esser-Nobis, Marco Binder, Ralf Bartenschlager, Mathias Heikenwälder, Philip Meuleman, Volker Lohmann
Journal: Journal of Hepatology (2023)

Hepatitis A virus (HAV) infections are considered not to trigger innate immunity in vivo, in contrast to hepatitis C virus (HCV). This lack of induction has been imputed to strong interference by HAV proteases 3CD and 3ABC. We aimed to elucidate the mechanisms of immune activation and counteraction by HAV and HCV in vivo and in vitro.Albumin-urokinase-type plasminogen activator/severe combined immunodeficiency (Alb/uPA-SCID) mice with humanised livers were infected with HAV and HCV. Hepatic cell culture models were used to assess HAV and HCV sensing by Toll-like receptor 3 and retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 (RIG-I/MDA5), respectively. Cleavage of the adaptor proteins TIR-domain-containing adapter-inducing interferon-β (TRIF) and mitochondrial antiviral-signalling protein (MAVS) was analysed by transient and stable expression of HAV and HCV proteases and virus infection.We detected similar levels of interferon-stimulated gene induction in hepatocytes of HAV- and HCV-infected mice with humanised liver. In cell culture, HAV induced interferon-stimulated genes exclusively upon MDA5 sensing and depended on LGP2 (laboratory of genetics and physiology 2). TRIF and MAVS were only partially cleaved by HAV 3ABC and 3CD, not sufficiently to abrogate signalling. In contrast, HCV NS3-4A efficiently degraded MAVS, as previously reported, whereas TRIF cleavage was not detected.HAV induces an innate immune response in hepatocytes via MDA5/LGP2, with limited control of both pathways by proteolytic cleavage. HCV activates Toll-like receptor 3 and lacks TRIF cleavage, suggesting that this pathway mainly contributes to HCV-induced antiviral responses in hepatocytes. Our results shed new light on the induction of innate immunity and counteraction by HAV and HCV.Understanding the mechanisms that determine the differential outcomes of HAV and HCV infections is crucial for the development of effective therapies. Our study provides insights into the interplay between these viruses and the host innate immune response in vitro and in vivo, shedding light on previously controversial or only partially investigated aspects. This knowledge could tailor the development of new strategies to combat HCV persistence, as well as improve our understanding of the factors underlying successful HAV clearance.
The Proteome Landscape of Human Placentas for Monochorionic Twins with Selective Intrauterine Growth Restriction
Authors: Xin-Lu Meng, Peng-Bo Yuan, Xue-Ju Wang, Jing Hang, Xiao-Ming Shi, Yang-Yu Zhao, Yuan Wei
Journal: Genomics Proteomics & Bioinformatics (2023)

Abstract In perinatal medicine, intrauterine growth restriction (IUGR) is one of the greatest challenges. The etiology of IUGR is multifactorial, but most cases are thought to arise from placental insufficiency. However, identifying the placental cause of IUGR can be difficult due to numerous confounding factors. Selective IUGR (sIUGR) would be a good model to investigate how impaired placentation affects fetal development, as the growth discordance between monochorionic twins cannot be explained by confounding genetic or maternal factors. Herein, we constructed and analyzed the placental proteomic profiles of IUGR twins and normal cotwins. Specifically, we identified a total of 5481 proteins, of which 233 were differentially expressed (57 up-regulated and 176 down-regulated) in IUGR twins. Bioinformatics analysis indicates that these differentially expressed proteins (DEPs) are mainly associated with cardiovascular system development and function, organismal survival, and organismal development. Notably, 34 DEPs are significantly enriched in angiogenesis, and diminished placental angiogenesis in IUGR twins has been further elaborately confirmed. Moreover, we found decreased expression of metadherin (MTDH) in the placentas of IUGR twins and demonstrated that MTDH contributes to placental angiogenesis and fetal growth in vitro. Collectively, our findings reveal the comprehensive proteomic signatures of placentas for sIUGR twins, and the DEPs identified may provide in-depth insights into the pathogenesis of placental dysfunction and subsequent impaired fetal growth.
Dissecting the KNDy hypothesis: KNDy neuron-derived kisspeptins are dispensable for puberty but essential for preserved female fertility and gonadotropin pulsatility
Authors: Inmaculada Velasco, Delphine Franssen, Silvia Daza-Dueñas, Katalin Skrapits, Szabolcs Takács, Encarnación Torres, Elvira Rodríguez-Vazquez, Miguel Ruiz-Cruz, Silvia León, Krisztina Kukoricza, Fu-Ping Zhang, Suvi Ruohonen, Diego Luque-Cordoba, Feliciano Priego-Capote, Francisco Gaytan, Francisco Ruiz-Pino, Erik Hrabovszky, Matti Poutanen, María J. Vázquez, Manuel Tena-Sempere
Journal: Metabolism (2023)
An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography
Authors: Jia-xu Liang, Javier Ampuero, Hao Niu, Kento Imajo, Mazen Noureddin, Jaideep Behari, Dae Ho Lee, Richard L. Ehman, Fredrik Rorsman, Johan Vessby, Juan R. Lacalle, Ferenc E. Mózes, Michael Pavlides, Quentin M. Anstee, Stephen A. Harrison, Javier Castell, Rohit Loomba, Manuel Romero-Gómez
Journal: Journal of Hepatology (2023)

We conducted an individual patient data meta-analysis to establish stiffness cut-off values for magnetic resonance elastography (MRE) in staging liver fibrosis and to assess potential confounding factors.
“Nocturia and obstructive sleep apnea syndrome: A systematic review”
Authors: Francesco Di Bello, Luigi Napolitano, Marco Abate, Claudia Collà Ruvolo, Simone Morra, Gianluigi Califano, Marco Capece, Massimiliano Creta, Cristiano Scandurra, Benedetta Muzii, Claudio Di Nola, Vincenzo Bochicchio, Riccardo Nocini, Vincenzo Abbate, Nelson Mauro Maldonato, Giovanni Dell’Aversana Orabona, Nicola Longo, Elena Cantone
Journal: Sleep Medicine Reviews (2023)

Lower urinary tract symptoms represent a significant public health problem worldwide, impairing patients' quality of life, especially in elderly people. Among LUTS, nocturia is assessed as the most experienced entity related to several disorders such as sleep disorders and/or obstructive sleep apnea syndrome (OSAS). Among OSAS patients, nocturia stands as a bothersome symptom that increases alongside with the OSAS severity. However, despite the nocturia and OSAS shared a long-acknowledged link, the causes, and the pathophysiology for development of nocturia in OSAS have remained largely unexamined. Generally, the patients with OSAS experienced nocturia due to easy waking or increased bladder filling. However, nor the effect of treatment on management of nocturia in OSAS patients are well-established.
Immunogenicity and safety of fractional doses of 17D-213 yellow fever vaccine in children (YEFE): a randomised, double-blind, non-inferiority substudy of a phase 4 trial
Authors: Aitana Juan-Giner, Maria L Namulwana, Derick Kimathi, Kyra H Grantz, Gamou Fall, Moussa Dia, Ndeye S Bob, Amadou Alpha Sall, Caroline Nerima, Mateus Kambale Sahani, Edgar M Mulogo, Immaculate Ampeire, Joachim Hombach, Deborah Nanjebe, Juliet Mwanga-Amumpaire, Derek A T Cummings, Philip Bejon, George M Warimwe, Rebecca F Grais
Journal: The Lancet Infectious Diseases (2023)